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https://www.readbyqxmd.com/read/28644435/p53-amyloid-formation-leading-to-its-loss-of-function-implications-in-cancer-pathogenesis
#1
Saikat Ghosh, Shimul Salot, Shinjinee Sengupta, Ambuja Navalkar, Dhiman Ghosh, Reeba Jacob, Subhadeep Das, Rakesh Kumar, Narendra Nath Jha, Shruti Sahay, Surabhi Mehra, Ganesh M Mohite, Santanu K Ghosh, Mamata Kombrabail, Guruswamy Krishnamoorthy, Pradip Chaudhari, Samir K Maji
The transcriptional regulator p53 has an essential role in tumor suppression. Almost 50% of human cancers are associated with the loss of p53 functions, where p53 often accumulates in the nucleus as well as in cytoplasm. Although it has been previously suggested that amyloid formation could be a cause of p53 loss-of-function in subset of tumors, the characterization of these amyloids and its structure-function relationship is not yet established. In the current study, we provide several evidences for the presence of p53 amyloid formation (in human and animal cancer tissues); along with its isolation from human cancer tissues and the biophysical characterization of these tissue-derived fibrils...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644178/temporal-thinning-in-sickle-cell-retinopathy-is-associated-with-diminished-perfusion-on-octa-and-dense-scotoma-on-microperimetery
#2
Kumar Sambhav, Sandeep Grover, Kakarla V Chalam
PURPOSE: To establish correlation between the structural compromise (capillary loss and hypoperfusion on optical coherence tomography [optical coherence tomography angiography]) with perimacular functional impairment noted on microperimetry. METHODS: Retrospective case series. Clinical records and multimodal imaging findings of patients presenting with sickle cell disease were reviewed. RESULTS: Three eyes of three patients (two men) were included in the study with a visual acuity of 20/20 and no sickle cell retinopathy...
June 20, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28644129/anti-cd47-antibodies-induce-phagocytosis-of-live-malignant-b-cells-by-macrophages-via-the-fc-domain-resulting-in-cell-death-by-phagoptosis
#3
Lucy E Métayer, Anna Vilalta, G A Amos Burke, Guy C Brown
When expressed on the surface of cells, CD47 inhibits phagocytosis of these cells by phagocytes. Most human cancers overexpress CD47, and antibodies to CD47 have shown a remarkable ability to clear a range of cancers in animal models. However, the mechanism by which these antibodies cause cancer cell death is unclear. We find that CD47 is expressed on the surface of three B-cell lines from human malignancies: 697 (pre-B-ALL lymphoblasts), Ramos and DG-75 (both mature B-cells, Burkitt's lymphoma), and anti-CD47 antibodies greatly increase the phagocytosis of all three cell line by macrophages...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643929/in-silico-and-functional-evaluation-of-pth1r-mutations-found-in-patients-with-primary-failure-of-eruption-pfe
#4
H M Hendricks, S Bencharit, W Seaman, S A Frazier-Bowers
OBJECTIVES: The genetic basis of PFE (OMIM ID: 125350) was interrogated using molecular functional studies. PFE is a disorder that results in a poor prognosis in the eruption of teeth and by extension, in treatment with a continuous archwire. We tested the hypothesis that PTH1R mutations result in loss of function due to altered protein structure to determine (i) the fate of a functional PTH1R mutation and (ii) the resulting PTH1R protein structure of each functional mutation. METHODS: We used immunofluorescence assay of COS7 cells that were transfected with either the WT or 1092delG PTH1R mutation sequence to compare the fate of the expressed protein...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643182/fvstr1-a-striatin-orthologue-in-fusarium-virguliforme-is-required-for-asexual-development-and-virulence
#5
Kazi T Islam, Jason P Bond, Ahmad M Fakhoury
The soil-borne fungus Fusarium virguliforme causes sudden death syndrome (SDS), one of the most devastating diseases of soybean in North and South America. Despite the importance of SDS, a clear understanding of the fungal pathogenicity factors that affect the development of this disease is still lacking. We have identified FvSTR1, a F. virguliforme gene, which encodes a protein similar to a family of striatin proteins previously reported to regulate signalling pathways, cell differentiation, conidiation, sexual development, and virulence in filamentous fungi...
June 22, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28642151/the-role-of-the-lb-structural-loop-and-its-interactions-with-the-pdz-domain-of-the-human-htra3-protease
#6
Tomasz Wenta, Przemysław Glaza, Mirosław Jarząb, Urszula Zarzecka, Dorota Żurawa-Janicka, Adam Lesner, Joanna Skórko-Glonek, Barbara Lipińska
Human HtrA3 protease is a proapoptotic protein, involved in embryo implantation and oncogenesis. In stress conditions the protease is activated by removal of its N-terminal domain. The activated form, ΔN-HtrA3L is a homotrimer composed of the protease (PD) and PDZ domains. The LB structural loop of the PD is longer by six amino acid residues than its counterparts of other human HtrA proteins and interacts with the PDZ in a way not observed in other known HtrA structures. By size exclusion chromatography of the ΔN-HtrA3L mutated variants we found that removal of the additional LB loop residues caused a complete loss of the proper trimeric structure while impairing their interactions with the PDZ domain decreased the amount of the trimers...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28640659/phlda1-pleckstrin-homology-like-domain-family-a-member-1-knockdown-promotes-migration-and-invasion-of-mcf10a-breast-epithelial-cells
#7
Naieli Bonatto, Maria José Carlini, Simone Aparecida de Bessa Garcia, Maria Aparecida Nagai
PHLDA1 (pleckstrin homology-like domain, family A, member 1) is a multifunctional protein that plays distinct roles in several biological processes including cell death and therefore its altered expression has been identified in different types of cancer. Progressively loss of PHLDA1 was found in primary and metastatic melanoma while its overexpression was reported in intestinal and pancreatic tumors. Previous work from our group showed that negative expression of PHLDA1 protein was a strong predictor of poor prognosis for breast cancer disease...
June 22, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28639250/regulation-of-nephrin-phosphorylation-in-diabetes-and-chronic-kidney-injury
#8
Benoit Denhez, Pedro Geraldes
Diabetes is the leading cause of microalbuminuria and end-stage renal failure in industrial countries. Disruption of the filtration barrier, seen in almost all nephrotic diseases and diabetes, is the result of the loss or effacement of the podocyte foot process, notably damage of proteins within the slit diaphragm such as nephrin. For many years, nephrin has been viewed as a structural component of the slit diaphragm. It is now well recognized that nephrin contains several tyrosine residues in its cytoplasmic domain, which influences the development of glomerular injury...
June 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28639158/development-of-a-survivorship-needs-assessment-planning-tool-for-head-and-neck-cancer-survivors-and-their-caregivers-a-preliminary-study
#9
K R Sterba, J Zapka, N LaPelle, T K Garris, A Buchanan, M Scallion, T Day
PURPOSE: The purpose of this study was to characterize primary end-of-treatment challenges in head and neck cancer (HNC) to drive the development of a survivorship needs assessment planning (SNAP) tool and evaluate its acceptability and feasibility. METHODS: Using qualitative methods (focus groups, interviews), we identified physical, emotional, and social post-treatment challenges from the perspectives of survivors (N = 17), caregivers (N = 14), and healthcare providers (N = 14) and pretested the SNAP tool...
June 21, 2017: Journal of Cancer Survivorship: Research and Practice
https://www.readbyqxmd.com/read/28637900/activation-of-mouse-tcrb-uncoupling-runx1-function-from-its-cooperative-binding-with-ets1
#10
Jiang-Yang Zhao, Oleg Osipovich, Olivia I Koues, Kinjal Majumder, Eugene M Oltz
T lineage commitment requires the coordination of key transcription factors (TFs) in multipotent progenitors that transition them away from other lineages and cement T cell identity. Two important TFs for the multipotent progenitors to T lineage transition are RUNX1 and ETS1, which bind cooperatively to composite sites throughout the genome, especially in regulatory elements for genes involved in T lymphopoiesis. Activation of the TCR β (Tcrb) locus in committed thymocytes is a critical process for continued development of these cells, and is mediated by an enhancer, Eβ, which harbors two RUNX-ETS composite sites...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28637830/a-light-harvesting-complex-like-protein-in-maintenance-of-photosynthetic-components-in-chlamydomonas
#11
Lei Zhao, Dongmei Cheng, Xiahe Huang, Mei Chen, Luca Dall'Osto, Jiale Xing, Liyan Gao, Lingyu Li, Yale Wang, Roberto Bassi, Lianwei Peng, Yingchun Wang, Jean-David Rochaix, Fang Huang
Using a genetic approach we have identified and characterized a novel protein, named Msf1 (Maintenance Factor for PSI), which is required for the maintenance of specific components of the photosynthetic apparatus in the green alga Chlamydomonas reinhardtii. Msf1 belongs to the superfamily of light-harvesting complex (LHC) proteins with three trans-membrane domains and consensus chlorophyll binding sites. Loss of Msf1 leads to reduced accumulation of PSI and chlorophyll-binding proteins/complexes. Msf1 is a component of a thylakoid complex containing key enzymes of the tetrapyrrole biosynthetic pathway thus revealing a possible link between Msf1 and chlorophyll biosynthesis...
June 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28637190/evolution-of-the-sperm-methylome-of-primates-is-associated-with-retrotransposon-insertions-and-genome-instability
#12
Kei Fukuda, Yukihiro Inoguchi, Kenji Ichiyanagi, Tomoko Ichiyanagi, Yasuhiro Go, Masashi Nagano, Yojiro Yanagawa, Noboru Takaesu, Yasuyuki Ohkawa, Hiroo Imai, Hiroyuki Sasaki
Changes in gene expression resulting from epigenetic and/or genetic changes play an important role in the evolutionary divergence of phenotypes. To explore how epigenetic and genetic changes are linked during primate evolution, we have compared the genome-wide DNA methylation profiles (methylomes) of humans and chimpanzees, which have a 1.2% DNA sequence divergence, of sperm, the frontal cortices, B cells, and neutrophils. We revealed that species-specific differentially methylated regions (S-DMRs), ranging from several hundred bp to several kb, were frequently associated with sequence changes in transcription factor binding sites and insertions of Alu and SVA retrotransposons...
June 20, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28635258/mucin-inspired-lubrication-on-hydrophobic-surfaces
#13
Benjamin Tillmann Käsdorf, Florian Weber, Georgia Petrou, Vaibhav Srivastava, Thomas Crouzier, Oliver Lieleg
In the human body, high molecular weight glycoproteins called mucins play a key role in protecting epithelial surfaces against pathogenic attack, controlling the passage of molecules towards the tissue and enabling boundary lubrication with very low friction coefficients. However, neither the molecular mechanisms nor the chemical motifs of those biomacromolecules involved in these fundamental processes are fully understood. Thus, identifying the key features that render biomacromolecules such as mucins outstanding boundary lubricants could set the stage for creating versatile artificial superlubricants...
June 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28634818/sg2na-is-a-regulator-of-endoplasmic-reticulum-er-homeostasis-as-its-depletion-leads-to-er-stress
#14
Buddhi Prakash Jain, Shweta Pandey, Nikhat Saleem, Goutam K Tanti, Shalini Mishra, Shyamal K Goswami
SG2NA belongs to a three-member striatin subfamily of WD40 repeat superfamily of proteins. It has multiple protein-protein interaction domains involved in assembling supramolecular signaling complexes. Earlier, we had demonstrated that there are at least five variants of SG2NA generated by alternative splicing, intron retention, and RNA editing. Such versatile and dynamic mode of regulation implicates it in tissue development. In order to shed light on its role in cell physiology, total proteome analysis was performed in NIH3T3 cells depleted of 78 kDa SG2NA, the only isoform expressing therein...
June 21, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28634442/mild-traumatic-brain-injury-evokes-pyramidal-neuron-axon-initial-segment-plasticity-and-diffuse-presynaptic-inhibitory-terminal-loss
#15
Michal Vascak, Jianli Sun, Matthew Baer, Kimberle M Jacobs, John T Povlishock
The axon initial segment (AIS) is the site of action potential (AP) initiation, thus a crucial regulator of neuronal activity. In excitatory pyramidal neurons, the high density of voltage-gated sodium channels (NaV1.6) at the distal AIS regulates AP initiation. A surrogate AIS marker, ankyrin-G (ankG) is a structural protein regulating neuronal functional via clustering voltage-gated ion channels. In neuronal circuits, changes in presynaptic input can alter postsynaptic output via AIS structural-functional plasticity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28634376/structural-basis-to-stabilize-the-domain-motion-of-bard1-ard-brct-by-cstf50
#16
Rajan Kumar Choudhary, Mohd Quadir Siddiqui, Pankaj S Thapa, Nikhil Gadewal, Senthil Kumar Nachimuthu, Ashok K Varma
BRCA1 associated ring domain protein 1(BARD1) is a tumor suppressor protein having a wide role in cellular processes like cell-cycle checkpoint, DNA damage repair and maintenance of genomic integrity. Germ-line mutation Gln 564 His discovered in linker region of BARD1 leads to loss of binding to Cleavage stimulating factor (CstF50), which in turn instigates the premature mRNA transcript formation and apoptosis. We have studied the dynamics of ARD domain present in the BARD1 wild-type and mutant protein in association with CstF50 using biophysical, biochemical and molecular dynamics simulations...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634088/duration-of-untreated-psychosis-and-neurocognition-in-first-episode-psychosis-a-meta-analysis
#17
REVIEW
Emre Bora, Berna Yalincetin, Berna Binnur Akdede, Koksal Alptekin
Neurocognitive impairment is a well-established feature of first-episode psychosis (FEP). Neurotoxicity hypothesis of psychosis suggests that untreated psychosis before the initiation of first effective treatment is associated with loss of acquired cognitive abilities. However, the outcome of the studies investigating the relationship between duration of untreated psychosis (DUP) and cognitive impairment in FEP remains inconclusive. No previous meta-analysis investigating the relationship between DUP and cognitive impairment in FEP has been published...
June 17, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28633361/evolution-of-mirna-tailing-by-3-terminal-uridylyl-transferases-in-metazoa
#18
Vengamanaidu Modepalli, Yehu Moran
In bilaterian animals the 3' ends of microRNAs (miRNAs) are frequently modified by tailing and trimming. These modifications affect miRNA-mediated gene regulation by modulating miRNA stability. Here we analyzed data from three non-bilaterian animals: two cnidarians (Nematostella vectensis and Hydra magnipapillata) and one poriferan (Amphimedon queenslandica). Our analysis revealed that non-bilaterian miRNAs frequently undergo modifications like the bilaterian counterparts: the majority are expressed as different length isoforms and frequent modifications of the 3' end by mono U or mono A tailing are observed...
June 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28633194/moving-forward-in-circles-challenges-and-opportunities-in-modelling-population-cycles
#19
REVIEW
Frédéric Barraquand, Stilianos Louca, Karen C Abbott, Christina A Cobbold, Flora Cordoleani, Donald L DeAngelis, Bret D Elderd, Jeremy W Fox, Priscilla Greenwood, Frank M Hilker, Dennis L Murray, Christopher R Stieha, Rachel A Taylor, Kelsey Vitense, Gail S K Wolkowicz, Rebecca C Tyson
Population cycling is a widespread phenomenon, observed across a multitude of taxa in both laboratory and natural conditions. Historically, the theory associated with population cycles was tightly linked to pairwise consumer-resource interactions and studied via deterministic models, but current empirical and theoretical research reveals a much richer basis for ecological cycles. Stochasticity and seasonality can modulate or create cyclic behaviour in non-intuitive ways, the high-dimensionality in ecological systems can profoundly influence cycling, and so can demographic structure and eco-evolutionary dynamics...
June 20, 2017: Ecology Letters
https://www.readbyqxmd.com/read/28632405/reading-performance-improvements-in-patients-with-central-vision-loss-without-age-related-macular-degeneration-after-undergoing-personalized-rehabilitation-training
#20
María B Coco-Martín, Alberto López-Miguel, Rubén Cuadrado, Agustín Mayo-Iscar, Azael J Herrero, José C Pastor, Miguel J Maldonado
PURPOSE: To evaluate the efficacy of a reading rehabilitation program (RRP) in patients with central visual loss (CVL) and assess the impact of the RRP on the quality of life (QoL). METHODS: The RRP included four in-office and 39 in-home training sessions over 6 weeks. Reading speed, duration, and font size were evaluated during each in-office session. The subjective perception of the QoL was assessed before and after the RRP using the short version of a questionnaire (World Health Organization Quality of Life)...
June 20, 2017: Current Eye Research
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